NOG

noggin

Basic information

Region (hg38): 17:56593698-56595611

Previous symbols: [ "SYNS1", "SYM1" ]

Links

ENSG00000183691 ∙ NCBI:9241 ∙ OMIM:602991 ∙ HGNC:7866 ∙ Uniprot:Q13253 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple synostoses syndrome 1 (Definitive), mode of inheritance: AD
• tarsal-carpal coalition syndrome (Supportive), mode of inheritance: AD
• multiple synostoses syndrome (Supportive), mode of inheritance: AD
• proximal symphalangism (Supportive), mode of inheritance: AD
• brachydactyly type B2 (Supportive), mode of inheritance: AD
• stapes ankylosis with broad thumbs and toes (Supportive), mode of inheritance: AD
• multiple synostoses syndrome 1 (Strong), mode of inheritance: AD
• NOG-related symphalangism spectrum disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brachydactyly, type B2; Tarsal-carpal coalition syndrome; Multiple synostosis syndrome 1; Symphalangism, proximal, 1A; Stapes ankylosis with broad thumb and toes (Teunissen-Cremers syndrome)	AD	Audiologic/Otolaryngologic	Hearing impairment may be prelingual in some individuals, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal	7245852; 6638061; 4019538; 10080184; 10069712; 11545688; 1846737; 12089654; 15770128; 16532400; 17668388; 18440889; 20503332; 19471170; 20503332; 21358557; 21538686; 22855651
Some conditions may be frequently recognizable based on clinical manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOG gene.

• not provided (101 variants)
• Inborn genetic diseases (7 variants)
• Proximal symphalangism 1A (5 variants)
• not specified (3 variants)
• Tarsal-carpal coalition syndrome (3 variants)
• Brachydactyly type B2 (2 variants)
• Stapes ankylosis with broad thumbs and toes (2 variants)
• NOG-related condition (2 variants)
• NOG-related-symphlangism spectrum disorder (1 variants)
• Symphalangism-brachydactyly syndrome (1 variants)
• Brachydactyly type B2;Symphalangism-brachydactyly syndrome;Tarsal-carpal coalition syndrome;Stapes ankylosis with broad thumbs and toes;Proximal symphalangism 1A (1 variants)
• NOG-related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOG gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	29		31
missense	4	5	51	2	2	64
nonsense	3	3	1			7
start loss						0
frameshift	3	1				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					5	5
Total	10	9	54	31	7

Variants in NOG

This is a list of pathogenic ClinVar variants found in the NOG region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-56593839-C-A			Benign (Apr 29, 2019)
17-56594151-G-A			Benign (Apr 29, 2019)
17-56594227-G-T		Inborn genetic diseases	Pathogenic (Feb 28, 2018)
17-56594229-G-A			Likely benign (Aug 23, 2022)
17-56594256-C-G			Likely benign (Aug 31, 2022)
17-56594262-C-A			Likely benign (Nov 03, 2022)
17-56594262-C-T			Likely benign (Nov 01, 2021)
17-56594263-C-T			Likely benign (Nov 19, 2022)
17-56594264-T-C		NOG-related-symphlangism spectrum disorder	Pathogenic (-)
17-56594265-G-A			Likely benign (Apr 06, 2023)
17-56594266-G-A			Uncertain significance (Jul 25, 2023)
17-56594266-G-T			Uncertain significance (Oct 24, 2023)
17-56594268-G-T			Likely benign (Nov 25, 2023)
17-56594271-G-A			Uncertain significance (Apr 10, 2023)
17-56594280-GC-G		Symphalangism-brachydactyly syndrome	Pathogenic (Dec 01, 2001)
17-56594284-C-CG		Symphalangism-brachydactyly syndrome	Pathogenic (Dec 06, 2019)
17-56594287-G-A			Uncertain significance (Jan 25, 2024)
17-56594290-A-G		Inborn genetic diseases	Likely benign (Apr 07, 2023)
17-56594291-C-T		not specified	Benign (Jan 04, 2024)
17-56594293-C-T			Benign (Jun 19, 2023)
17-56594298-C-T			Likely benign (May 27, 2023)
17-56594301-C-T			Likely benign (Jan 19, 2024)
17-56594312-A-T		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
17-56594319-C-T			Likely benign (Sep 04, 2023)
17-56594324-G-C		Proximal symphalangism 1A	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOG	protein_coding	protein_coding	ENST00000332822	1	1892

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.890	0.109	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	94	137	0.684	0.00000614	1459
Missense in Polyphen		17	55.005	0.30906		578
Synonymous	-0.560	72	66.2	1.09	0.00000306	505
Loss of Function	2.48	0	7.17	0.00	3.10e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite. Essential for cartilage morphogenesis and joint formation. Inhibits chondrocyte differentiation through its interaction with GDF5 and, probably, GDF6 (PubMed:21976273, PubMed:26643732). {ECO:0000269|PubMed:12478285, ECO:0000269|PubMed:21976273, ECO:0000269|PubMed:26643732}.
• Disease: DISEASE: Symphalangism, proximal 1A (SYM1A) [MIM:185800]: A disease characterized by the hereditary absence of the proximal interphalangeal joints. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conductive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone. {ECO:0000269|PubMed:10080184, ECO:0000269|PubMed:11846737, ECO:0000269|PubMed:11857750, ECO:0000269|PubMed:15770128}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Multiple synostoses syndrome 1 (SYNS1) [MIM:186500]: A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism. {ECO:0000269|PubMed:10080184, ECO:0000269|PubMed:20503332}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Tarsal-carpal coalition syndrome (TCC) [MIM:186570]: Autosomal dominant disorder characterized by fusion of the carpals, tarsals and phalanges, short first metacarpals causing brachydactyly, and humeroradial fusion. TCC is allelic to SYM1, and different mutations in NOG can result in either TCC or SYM1 in different families. {ECO:0000269|PubMed:11545688}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stapes ankylosis with broad thumb and toes (SABTS) [MIM:184460]: An autosomal dominant disorder characterized by hyperopia, a hemicylindrical nose, broad thumbs, great toes, and other minor skeletal anomalies but lacked carpal and tarsal fusion and symphalangism. {ECO:0000269|PubMed:12089654}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Brachydactyly B2 (BDB2) [MIM:611377]: A form of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones and partial cutaneous syndactyly. {ECO:0000269|PubMed:17668388}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Bone Morphogenic Protein (BMP) Signalling and Regulation;Cardiac Progenitor Differentiation;Hair Follicle Development- Induction (Part 1 of 3);Differentiation Pathway;Endoderm Differentiation;Mesodermal Commitment Pathway;ESC Pluripotency Pathways;TGF-beta Receptor Signaling;Signal Transduction;alk in cardiac myocytes;BMP receptor signaling;Signaling by BMP;Signaling by TGF-beta family members (Consensus)

Recessive Scores

• pRec: 0.729

Intolerance Scores

• loftool: 0.0709
• rvis_EVS: 0.35
• rvis_percentile_EVS: 73.97

Haploinsufficiency Scores

• pHI: 0.773
• hipred: Y
• hipred_score: 0.759
• ghis: 0.424

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.651

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nog
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; taste/olfaction phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; vision/eye phenotype; craniofacial phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; respiratory system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: nog1
• Affected structure: Meckel's cartilage
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;osteoblast differentiation;in utero embryonic development;endoderm formation;mesoderm formation;epithelial to mesenchymal transition;neural plate morphogenesis;neural tube closure;membranous septum morphogenesis;outflow tract morphogenesis;endocardial cushion morphogenesis;ventricular compact myocardium morphogenesis;nervous system development;motor neuron axon guidance;dorsal/ventral pattern formation;positive regulation of gene expression;spinal cord development;cell differentiation in hindbrain;pituitary gland development;negative regulation of cell migration;BMP signaling pathway;negative regulation of BMP signaling pathway;somatic stem cell population maintenance;wound healing;middle ear morphogenesis;embryonic digit morphogenesis;negative regulation of osteoblast differentiation;positive regulation of transcription by RNA polymerase II;axial mesoderm development;notochord morphogenesis;embryonic skeletal system development;negative regulation of astrocyte differentiation;positive regulation of epithelial cell proliferation;cartilage development;atrial cardiac muscle tissue morphogenesis;negative regulation of cardiac muscle cell proliferation;limb development;embryonic skeletal joint morphogenesis;negative regulation of cytokine activity;face morphogenesis;negative regulation of pathway-restricted SMAD protein phosphorylation;ventricular septum morphogenesis;lung morphogenesis;prostatic bud formation;ureteric bud formation;fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation;negative regulation of cartilage development;somite development;BMP signaling pathway involved in heart development;heart trabecula morphogenesis;pharyngeal arch artery morphogenesis;negative regulation of canonical Wnt signaling pathway;positive regulation of branching involved in ureteric bud morphogenesis;positive regulation of glomerulus development;negative regulation of epithelial to mesenchymal transition involved in endocardial cushion formation;regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation;negative regulation of apoptotic signaling pathway
• Cellular component: extracellular region;extracellular space
• Molecular function: protein binding;cytokine binding;protein homodimerization activity